The purpose of this study was to quantify indices of regional bone metabolism in Paget's disease and to compare these indices with normal bone using dynamic 18F-fluoride positron emission tomography (PET). Seven patients with vertebral Paget's disease had 1 h dynamic 18F-fluoride PET scans performed. The scans included a diseased vertebra and an adjacent normal vertebra. Arterial plasma input functions were also measured. A three-compartment, four-parameter model was used with nonlinear regression analysis to estimate bone kinetic variables. Compared with normal bone, pagetic bone demonstrated higher values of plasma clearance to bone mineral (Ki; 1.03 x 10(-1) vs. 0.36 x 10(-1) ml/min per milliliter; p = 0.018) and clearance to total bone tissue (K1; 2.38 x 10(-1) vs. 1.25 x 10(-1) ml/min per milliliter; p = 0.018), reflecting increased mineralization and blood flow, respectively. Release of 18F-fluoride from bone mineral (k4) was lower in pagetic bone (p = 0.022), suggesting tighter binding of 18F-fluoride to bone mineral. The notional volume of the extravascular bone compartment (K1/k2) was greater in pagetic bone (p = 0.018). Although the unidirectional extraction efficiency from the extravascular space to bone mineral (Ki/K1) was greater in pagetic bone (p = 0.018), a lower pagetic value of k2 (p = 0.028), describing the rate of transfer from the bone extravascular compartment to plasma, suggests that the 18F-fluoride that enters the relatively fibrotic marrow space of pagetic bone may be less accessible for return to plasma. These findings confirm some of the known pathophysiology of Paget's disease, introduce some new observations, and show how dynamic 18F-fluoride PET may be of value in the measurement of regional metabolic parameters in focal bone disorders.